CN103182049B - Preparation method of pharmaceutical composition preparation treating apoplexy sequelae - Google Patents
Preparation method of pharmaceutical composition preparation treating apoplexy sequelae Download PDFInfo
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Abstract
The invention relates to a preparation method of a pharmaceutical composition preparation treating apoplexy sequelae. The method includes volatile oil extraction and inclusion, ethanol extraction, water extraction, medicinal fine powder crushing, preparation molding and other steps. Compared with traditional preparations, the medication compliance of patients can be improved obviously. Under the premise of retaining original preparation efficacy, the pharmaceutical preparation prepared by the method provided in the invention can realize rapid absorption, effective components can intensively reach nidi to take fast effect, and the bioavailability is high. The pharmaceutical preparation prepared by the method disclosed in the invention has improved efficacy.
Description
Technical field
The invention belongs to field of traditional Chinese, relate to a kind of preparation method for the treatment of the drug combination preparation of apoplexy sequela, particularly the preparation method of precious imperial refreshment pharmaceutical preparation.
Background technology
Apoplexy sequela is many by caused by acute cerebrovascular diseases, and acute cerebrovascular disease is the disease of common serious harm human health, claims again clinically apoplexy.It falls ill anxious, recovers but very slow, often leaves over dysfunction in various degree.Often with hemiplegia, numb limbs and tense tendons, pain contracture, have a dizzy spell, facial hemiparalysis, slurred speech, mortality rate is high, disability rate is high.
Precious imperial refreshment capsule records in Chinese patent medicine provincial standard rising national drug standards parts (internal medicine brain is meridians limbs fascicles); Standard number: WS-10708 (ZD-0708)-2002.Precious imperial refreshment capsule is by Margarita 17.3g, Concretio Silicea Bambusae 2.2g, Stigma Croci 8.7g, Flos Caryophylli 9.7g, Semen Myristicae 8.7g, Fructus Amomi Rotundus 8.7g, Fructus Tsaoko 6.5g, Lignum Santali Albi 8.7g, Lignum pterocarpi indici 21.6g, Lignum Aquilariae Resinatum 17.3g, Fructus Chebulae 28.1g, Fructus Terminaliae Billericae 17.3g, Fructus Phyllanthi 21.6g, Radix Aucklandiae 21.6g, Cortex Cinnamomi 17.3g, Fructus Piperis Longi 8.7g, Eriocheir sinensis 10.8g, Lapis Micae Aureus 8.7g, Cuminum celery 5.4g, artificial Calculus Bovis 2.2g, Moschus 2.2g, Fructus Choerospondiatis 6.5g, Rhododendron 6.5g, Corydalis impatiens (Pall.) Fisch. 13.0g, Lagotis brachystachya Maxim. 43.3g, iron powder (system) 4.3g, Fructus Malvae 17.3g, Radix Glycyrrhizae 13.0g, Semen Nigellae 5.4g forms.There is the refreshment of having one's ideas straightened out, the effect of heat clearing away dredging collateral.For the apoplexy due to phlegm stagnation in collateral, aphasia, hemiplegia, facial hemiparalysis.Due to respond well, through clinical verification, evident in efficacy, enjoy clinically patient to favor.Precious imperial refreshment capsule tradition preparation method is: get artificial Calculus Bovis, Moschus, Stigma Croci and be ground into fine powder, 20 Six-elements such as all the other Margaritas are ground into fine powder, sieve, and with above-mentioned fine powder facing-up, mix, and incapsulate, and obtain.CN1827155A (CN200510119871.6) also discloses a kind of consciousness-restoring granule with pearl, and crude drug is Margarita, Concretio Silicea Bambusae, 29 kinds of medical materials such as Stigma Croci; Manufacture method is to prepare burden in proportion by crude drug, then is ground into fine powder, and fine powder is mixed to rear granulation product.
The simple physical processing that prior art all adopts raw medicinal material pulverizing, mixes about the preparation method of the imperial refreshment medicine of treasure, raw material the effective elements of the medicine discharges slowly, badly influences absorbing of effective ingredient.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, a kind of preparation method for the treatment of the drug combination preparation of apoplexy sequela is provided.
Technical scheme of the present invention is as follows:
A kind of preparation method for the treatment of the drug combination preparation of apoplexy sequela, the raw material medicines in portions by weight of described pharmaceutical composition consists of: 17.3 parts of Margaritas, 2.2 parts of Concretio Silicea Bambusaes, 8.7 parts of Stigma Crocis, 9.7 parts of Flos Caryophyllis, 8.7 parts of Semen Myristicaes, 8.7 parts, Fructus Amomi Rotundus, 6.5 parts of Fructus Tsaokos, 8.7 parts, Lignum Santali Albi, 21.6 parts of Lignum pterocarpi indici, 17.3 parts of Lignum Aquilariae Resinatum, 28.1 parts of Fructus Chebulaes, 17.3 parts of Fructus Terminaliae Billericaees, 21.6 parts of Fructus Phyllanthis, 21.6 parts of the Radix Aucklandiae, 17.3 parts of Cortex Cinnamomis, 8.7 parts of Fructus Piperis Longi, 10.8 parts of Eriocheir sinensiss, 8.7 parts of Lapis Micae Aureuses, 5.4 parts of Cuminum celerys, 2.2 parts of artificial Calculus Boviss, 2.2 parts, Moschus, 6.5 parts of Fructus Choerospondiatis, 6.5 parts of Rhododendrons, 13.0 parts of Corydalis impatiens (Pall.) Fisch.s, 43.3 parts of Lagotis brachystachya Maxim.s, 4.3 parts of iron powders (system), 17.3 parts of Fructus Malvae, 13.0 parts, Radix Glycyrrhizae, 5.4 parts of Semen Nigellaes, comprise the following steps:
(1) by crude drug composition and ratio, get the totally 14 taste medical materials mixing of Fructus Piperis Longi, Flos Caryophylli, Semen Myristicae, Fructus Amomi Rotundus, Fructus Tsaoko, Cuminum celery, Lignum Santali Albi, Semen Nigellae, Lignum Aquilariae Resinatum, Fructus Malvae, Cortex Cinnamomi, the Radix Aucklandiae, Lignum pterocarpi indici, Rhododendron, by 4～8 water extraordinarily of 14 taste medical material gross weights, adopt steam distillation, extract volatile oil, extract 3～6h, collect volatile oil, obtain volatile oil, medicinal liquid filters, and obtains extracting solution A and medicinal residues A;
Gained volatile oil is added in the beta cyclodextrin saturated aqueous solution of percent weight in volume 3-4%, the envelope-bulk to weight ratio of volatile oil and beta cyclodextrin is 1ml: 3-5g, under stirring condition, keep 40 ℃-60 ℃ of temperature, stir 3～4h ,-4 ℃ of-4 ℃ of cold preservations are spent the night, sucking filtration, precipitation, 40 ℃ of-60 ℃ of vacuum dryings, obtain volatile oil clathrate compound;
(2) press crude drug composition and ratio extracting liquorice, Lagotis brachystachya Maxim., Fructus Choerospondiatis, Corydalis impatiens (Pall.) Fisch., Fructus Chebulae, Fructus Phyllanthi, Fructus Terminaliae Billericae totally 7 taste medical materials, medicinal residues A after extracting volatile oil with step (1) mixes, alcoholic solution reflux, extract, 2-3 time that adds volumetric concentration 60～100%, the amount that at every turn adds ethanol is described 7 taste medical materials and medicinal residues A gross weight 8-10 times, extracts 2-3h, filters, merge medicinal liquid and obtain ethanol extraction liquid, concentrating under reduced pressure, dry, obtain ethanol extraction and medicinal residues B;
(3) the medicinal residues B after above-mentioned steps (2) ethanol extraction, extracting in water 2-3 time, the weight that at every turn adds water is 8-10 times of medicinal residues B weight, extracts 2-3h, filters, and merges medicinal liquid and obtains extracting solution B; This extracting solution B and step (1) are extracted to the extracting solution A merging after volatile oil, and concentrating under reduced pressure, is concentrated into the fluid extract that under 60 ℃ of conditions, relative density is 1.12, dry, obtains water extract;
(4) by crude drug composition and ratio, get Margarita, Concretio Silicea Bambusae, Eriocheir sinensis, Lapis Micae Aureus, iron powder (system), Stigma Croci, artificial Calculus Bovis, Moschus totally 8 taste medical materials, pulverize, obtain medical material fine powder;
(5) volatile oil clathrate compound above-mentioned steps (1) being made to (4), ethanol extraction, water extract and medical material fine powder mix, and add conventional adjuvant, according to common process, are prepared into pharmaceutically acceptable any dosage form.
Preferably, the present invention treats the preparation method of the medicament composition capsule of apoplexy sequela, the raw material medicines in portions by weight of described pharmaceutical composition consists of: 17.3 parts of Margaritas, 2.2 parts of Concretio Silicea Bambusaes, 8.7 parts of Stigma Crocis, 9.7 parts of Flos Caryophyllis, 8.7 parts of Semen Myristicaes, 8.7 parts, Fructus Amomi Rotundus, 6.5 parts of Fructus Tsaokos, 8.7 parts, Lignum Santali Albi, 21.6 parts of Lignum pterocarpi indici, 17.3 parts of Lignum Aquilariae Resinatum, 28.1 parts of Fructus Chebulaes, 17.3 parts of Fructus Terminaliae Billericaees, 21.6 parts of Fructus Phyllanthis, 21.6 parts of the Radix Aucklandiae, 17.3 parts of Cortex Cinnamomis, 8.7 parts of Fructus Piperis Longi, 10.8 parts of Eriocheir sinensiss, 8.7 parts of Lapis Micae Aureuses, 5.4 parts of Cuminum celerys, 2.2 parts of artificial Calculus Boviss, 2.2 parts, Moschus, 6.5 parts of Fructus Choerospondiatis, 6.5 parts of Rhododendrons, 13.0 parts of Corydalis impatiens (Pall.) Fisch.s, 43.3 parts of Lagotis brachystachya Maxim.s, 4.3 parts of iron powders (system), 17.3 parts of Fructus Malvae, 13.0 parts, Radix Glycyrrhizae, 5.4 parts of Semen Nigellaes, comprise the following steps:
(1) by crude drug composition and ratio, get the totally 14 taste medical materials mixing of Fructus Piperis Longi, Flos Caryophylli, Semen Myristicae, Fructus Amomi Rotundus, Fructus Tsaoko, Cuminum celery, Lignum Santali Albi, Semen Nigellae, Lignum Aquilariae Resinatum, Fructus Malvae, Cortex Cinnamomi, the Radix Aucklandiae, Lignum pterocarpi indici, Rhododendron, by 6 water extraordinarily of 14 taste medical material gross weights, adopt steam distillation, extract volatile oil, extract 4h, collect volatile oil, obtain volatile oil, medicinal liquid filters, and obtains extracting solution A and medicinal residues A;
Gained volatile oil is added in the beta cyclodextrin saturated aqueous solution of percent weight in volume 4%, the envelope-bulk to weight ratio of volatile oil and beta cyclodextrin is 1ml: 4g, under stirring condition, keeps temperature 60 C, stir 4h, 4 ℃ of cold preservations are spent the night, sucking filtration, precipitation, 50 ℃ of vacuum dryings, obtain volatile oil clathrate compound;
(2) press crude drug composition and ratio extracting liquorice, Lagotis brachystachya Maxim., Fructus Choerospondiatis, Corydalis impatiens (Pall.) Fisch., Fructus Chebulae, Fructus Phyllanthi, Fructus Terminaliae Billericae totally 7 taste medical materials, medicinal residues A after extracting volatile oil with step (1) mixes, the ethanol water reflux, extract, 2 times that adds volumetric concentration 90%, the amount that adds for the first time ethanol is described 7 taste medical materials and medicinal residues A gross weight 10 times, extract 2h, the amount that adds for the second time ethanol is described 7 taste medical materials and medicinal residues A gross weight 8 times, extract 2h, filter, merge medicinal liquid and obtain ethanol extraction liquid, concentrating under reduced pressure, dry, obtain ethanol extraction and medicinal residues B;
(3) the medicinal residues B after above-mentioned steps (2) ethanol extraction, extracting in water 2 times, the weight that adds for the first time water is 10 times of parts of medicinal residues B weight, extract 2h, the weight that adds for the second time water is 8 times of medicinal residues B weight, extracts 2h, filters, merge medicinal liquid and obtain extracting solution B, this extracting solution B and step (1) are extracted to the extracting solution A merging after volatile oil, and concentrating under reduced pressure, is concentrated into the fluid extract that under 60 ℃ of conditions, relative density is 1.12, dry, obtain water extract;
(4) by crude drug composition and ratio, get Margarita, Concretio Silicea Bambusae, Eriocheir sinensis, Lapis Micae Aureus, iron powder (system), Stigma Croci, artificial Calculus Bovis, Moschus totally 8 taste medical materials, pulverize, obtain medical material fine powder;
(5) volatile oil clathrate compound above-mentioned steps (1) being made to (4), ethanol extraction, water extract and medical material fine powder mix, and add appropriate amount of starch, granulate, dry, incapsulate, and obtain.
The pass of weight portion of the present invention and parts by volume is g/ml or kg/l.
Feature of the present invention is to take plant composition as material base, take drug activity as guidance, take into full account the character of ingredient, different clinical disease needs, and the compliance of medication object and physiological conditions etc., adopt new extraction preparation method, prepare precious imperial refreshment pharmaceutical preparation, compare with conventional formulation, patient's medication compliance can obviously improve; Pharmaceutical preparation prepared by method of the present invention is retaining under the prerequisite of former preparation drug effect, can realize and absorbing soon, and effective ingredient is concentrated and arrived lesions position, and rapid-action, bioavailability is high.Detailed experimental data will be in the specific embodiment comparative illustration in addition.Pharmaceutical preparation prepared by the inventive method has improved curative effect.Meanwhile, the volatile oil component of the present invention to prescription medical material, extracts, and adopts beta cyclodextrin clathrate process.
The specific embodiment
Following embodiment and experimental example are used for further illustrating but are not limited to the present invention.The treasure dragon refreshment novel formulation of using in experimental example is the pharmaceutical composition of the treatment apoplexy sequela prepared of the inventive method.
The raw material medicines in portions by weight proportioning of embodiment 1-4 pharmaceutical composition is as follows:
17.3 parts of Margaritas, 2.2 parts of Concretio Silicea Bambusaes, 8.7 parts of Stigma Crocis, 9.7 parts of Flos Caryophyllis, 8.7 parts of Semen Myristicaes, 8.7 parts, Fructus Amomi Rotundus, 6.5 parts of Fructus Tsaokos, 8.7 parts, Lignum Santali Albi, 21.6 parts of Lignum pterocarpi indici, 17.3 parts of Lignum Aquilariae Resinatum, 28.1 parts of Fructus Chebulaes, 17.3 parts of Fructus Terminaliae Billericaees, 21.6 parts of Fructus Phyllanthis, 21.6 parts of the Radix Aucklandiae, 17.3 parts of Cortex Cinnamomis, 8.7 parts of Fructus Piperis Longi, 10.8 parts of Eriocheir sinensiss, 8.7 parts of Lapis Micae Aureuses, 5.4 parts of Cuminum celerys, 2.2 parts of artificial Calculus Boviss, 2.2 parts, Moschus, 6.5 parts of Fructus Choerospondiatis, 6.5 parts of Rhododendrons, 13.0 parts of Corydalis impatiens (Pall.) Fisch.s, 43.3 parts of Lagotis brachystachya Maxim.s, 4.3 parts of iron powders (system), 17.3 parts of Fructus Malvae, 13.0 parts, Radix Glycyrrhizae, 5.4 parts of Semen Nigellaes.
The imperial refreshment capsule of the former commercially available treasure of use is that Qinghai gold is scolded Tibetan medicine Pharmaceutical limited company product, lot number: 20090908 as a comparison.
Embodiment 1, a kind of preparation for the treatment of the medicament composition capsule of apoplexy sequela
(1) volatile oil extracts and enclose: by crude drug composition and ratio, get Fructus Piperis Longi 435g, Flos Caryophylli 485g, Semen Myristicae 435g, Fructus Amomi Rotundus 435g, Fructus Tsaoko 325g, Cuminum celery 270g, Lignum Santali Albi 435g, Semen Nigellae 270g, Lignum Aquilariae Resinatum 865g, Fructus Malvae 865g, Cortex Cinnamomi 865g, Radix Aucklandiae 1080g, Lignum pterocarpi indici 1080g, Rhododendron 325g totally 14 taste medical materials mixing, by 6 water extraordinarily of 14 taste medical material gross weights, adopt steam distillation, extract volatile oil, extract 4h, collect volatile oil, obtain volatile oil, medicinal liquid filters, and obtains extracting solution A and medicinal residues A;
Gained volatile oil is added in the beta cyclodextrin saturated aqueous solution of percent weight in volume 4%, the envelope-bulk to weight ratio of volatile oil and beta cyclodextrin is 1ml: 4g, under stirring condition, keeps temperature 60 C, stir 4h, 4 ℃ of cold preservations are spent the night, sucking filtration, precipitation, 50 ℃ of vacuum dryings, obtain volatile oil clathrate compound;
(2) ethanol extraction: press crude drug composition and ratio extracting liquorice 650g, Lagotis brachystachya Maxim. 2165g, Fructus Choerospondiatis 325g, Corydalis impatiens (Pall.) Fisch. 650g, Fructus Chebulae 1405g, Fructus Phyllanthi 1080g, Fructus Terminaliae Billericae 865g is totally 7 taste medical materials, medicinal residues A after extracting volatile oil with step (1) mixes, the ethanol water reflux, extract, 2 times that adds volumetric concentration 90%, the amount that adds for the first time ethanol is described 7 taste medical materials and medicinal residues A gross weight 10 times, extract 2h, the amount that adds for the second time ethanol is described 7 taste medical materials and medicinal residues A gross weight 8 times, extract 2h, filter, merge medicinal liquid and obtain ethanol extraction liquid, concentrating under reduced pressure, dry, obtain ethanol extraction and medicinal residues B,
(3) water extraction: the medicinal residues B after above-mentioned steps (2) ethanol extraction, extracting in water 2 times, the weight that adds for the first time water is 10 times of parts of medicinal residues B weight, extract 2h, the weight that adds for the second time water is 8 times of medicinal residues B weight, extracts 2h, filters, merge medicinal liquid and obtain extracting solution B, this extracting solution B and step (1) are extracted to the extracting solution A merging after volatile oil, and concentrating under reduced pressure, is concentrated into the fluid extract that under 60 ℃ of conditions, relative density is 1.12, dry, obtain water extract;
(4) medical material fine powder is pulverized: by crude drug composition and ratio, get Margarita 865g, Concretio Silicea Bambusae 110g, Eriocheir sinensis 540g, Lapis Micae Aureus 435g, iron powder (system) 215g, Stigma Croci 435g, artificial Calculus Bovis 110g, Moschus 110g totally 8 taste medical materials, pulverize, obtain medical material fine powder;
(5) preparations shaping: the volatile oil clathrate compound that above-mentioned steps (1) is obtained to (4), ethanol extraction, water extract and medical material fine powder mix, get Zhen Long refreshment extract, according to common process, add appropriate amount of starch, granulate, dry Installed becomes 0.3g/ capsules, obtains.
Experimental example 1, the novel formulation of above-described embodiment 1 is carried out to neural cell injury protective effect contrast experiment together with treasure's original preparation of imperial refreshment capsule and positive control medicine
One, experiment material:
1, the precious imperial refreshment capsule of the preparation of precious imperial refreshment capsule novel formulation: embodiment 1;
2, the former preparation of precious imperial refreshment capsule (hereinafter to be referred as former preparation): the imperial refreshment capsule of commercially available treasure (Qinghai gold is scolded Tibetan medicine Pharmaceutical limited company), lot number: 20090908.
3, positive control medicine: FUFANG DANSHEN DIWAN, Tianjin Tian Shili pharmaceutical Co. Ltd, lot number: 100413.
4, cell line: PC12 cell line (source: Ratt μ s norvegic μ s Adrenal Pheochromocytoma, Nanjing KaiJi Biology Science Development Co., Ltd provides).
5, reagent: H-DMEM cell culture medium (Hyclone, Sai Mo flies generation that biochemistry goods Beijing company limited); Hyclone (Israel Bioind); Pancreatin cell dissociation buffer (the green skies), penicillin streptomycin mixed liquor is dual anti-, cisplatin for inj (Qilu Pharmaceutical Co., Ltd., 1010041DC), citrate buffer (Beijing Bioisystech Co., Ltd of Zhong Shan Golden Bridge), paraformaldehyde (solarbio), Pidolidone (Klonetech, Japan).
6, experimental apparatus
Vertical pressure steam sterilization pan (LDZX-50FBS, Shen, Shanghai peace); Double one side clean work station (SW-CJ-1C, Suzhou purifies); CO2 gas incubator (BB16 μ V/BB5060 μ V, HERAE μ S); Desk centrifuge (H3, Sigma); Microplate reader (M μ ltiskan MK3, Thermo Scientific); Electric heating constant-temperature blowing drying box (101, Shanghai Peng Shun scientific instrument company limited); Inverted microscope (XDS-1B, optical instrument factory, Chongqing); Water-bath constant temperature oscillator (SHZ-82, Jintan City Medical Instruments factory); Pipettor (Gilson, Eppendorf); Culture bottle (Corning); 96 orifice plates (Costar, μ SA)
Two, experimental technique
1. model preparation
The PC12 cell recovery of getting cryopreservation, is inoculated in culture bottle, with the H-DMEM culture medium culturing containing 10% hyclone.When the fusion of PC12 Growth of Cells to 80%, the pancreatin cell dissociation buffer with 0.25% (containing 0.02%EDTA) digests, and cell counting, adjusts cell density, the cell of suitable density is inoculated in 96 orifice plates to 1 * 10
4individual cells/well, zeroing hole does not add cell.Put 37 ℃, 5%CO
2incubator is cultivated.After the cell attachment monolayer in 96 orifice plates covers with, discard culture medium, aseptic PBS liquid cleans 2 times, except zeroing group, Normal group, it is that the glutamic acid (being dissolved in incomplete culture medium) of 30mmol/l continues to cultivate 24h in incubator that every hole adds final concentration, causes PC12 cell injury model.
2. experiment grouping
96 orifice plates are divided into Normal group, model group, positive drug group, the former preparation high and low dose of precious imperial refreshment group, precious imperial refreshment novel formulation high and low dose group, totally 7 groups, every group of 12 holes.
3. experiment administration
Discard the Glu-induced Injury cell culture fluid of cultivation, with aseptic PBS liquid, clean 2 times, the every hole of administration group adds respectively the DMEM culture medium 100 μ l that are followed successively by 10 μ g/ml, 1 μ g/ml containing screening of medicaments final concentration.Blank group adds equal-volume not containing the DMEM culture medium of medicine, and it is 27mg/ml FUFANG DANSHEN DIWAN serum-free DMEM culture medium 100 μ l that positive controls adds final concentration.Each concentration medicine adds 12 holes.The cell of administration reparation is put and in 37 ℃, 5%CO2 incubator, continued to cultivate 24h.
Three, index determining
1.MTT method is measured cell viability
Cell discards after unnecessary culture fluid, and every hole adds 100 μ l serum-free DMEM culture medium, adds 5mg/mlMTT solution 20 μ l, lucifuge reaction 4h in incubator.Discard again culture fluid, add dimethyl sulfoxide (DMSO) 100 μ l, mix.By microplate reader, in 570nm, measure optical density (OD) value, calculate cell survival rate.Computing formula: cell survival rate (%)=(medication group or model group A570/ control group A 570) * 100%.
2.NO, LDH, SOD assay
Cell injury administration was cultivated after 24 hours, with sterile tube collecting cell supernatant, centrifugal 20 minutes (2000r/min), careful collecting cell supernatant, by corresponding reagent box description time-and-motion study NO, LDH, SOD content.
Four. experimental result
1, the impact of precious imperial refreshment capsule on the PC12 cell survival rate of damage
The result that the precious imperial refreshment capsule of table 1 affects the PC12 cell survival rate of damage (
n=12)
Note: compare * P < 0.05 with model group; Compare #P < 0.05 with former preparation high dose
The demonstration of table 1 result, compares with model group, and final concentration is 1 μ g/ml, and the novel formulation of 10 μ g/ml and former preparation cell survival rate increase, and P < 0.05, all has significant difference; Embodiment 1 novel formulation high dose group is compared with former preparation high dose, and survival rate increases, and P < 0.05, has significant difference.Prompting novel formulation is being better than former preparation aspect enhancing cell viability.
2, the impact of precious imperial refreshment capsule on the NO content of PC12 cell
The precious imperial refreshment capsule of table 2 on the impact of the NO content of PC12 cell (
n=12)
Note: compare * P < 0.05 with model group
The demonstration of table 2 result, with model group comparison, the high low dose group NO content of novel formulation reduces, and has significant difference.The high low dose group NO content of former preparation there was no significant difference.Prompting novel formulation can reduce PC12 cell NO content, and is better than former preparation.
3, the impact of precious imperial refreshment capsule on the PC12 cell LDH content of In vitro culture
The precious imperial refreshment capsule of table 3 on PC12 cell LDH impact (
n=12)
Note: compare * P < 0.05 with model group; Compare #P < 0.05 with dosage groups such as former preparations.Wherein, IU/L be iu/liter.
The demonstration of table 3 result, compares with model group, and novel formulation and former preparation high dose can reduce the PC12 cell LDH content of In vitro culture, and P < 0.05, all has significant difference; Embodiment 1 novel formulation high dose group is compared with former preparation high dose group, and LDH content is lower, and P < 0.05, has significant difference.Prompting reduce LDH horizontal aspect, novel formulation is better than former preparation.
4, the impact of precious imperial refreshment capsule on the PC12 cell SOD content of In vitro culture
The precious imperial refreshment capsule of table 4 on the impact of PC12 cell SOD content (
n=12)
Note: compare * P < 0.05 with model group
The demonstration of table 4 result, compares with model group, and novel formulation high and low dose all can reduce the PC12 cell SOD content of In vitro culture, and P < 0.05, all has significant difference, former preparation there was no significant difference; Prompting increased SOD horizontal aspect, novel formulation is better than former preparation.
Five, experiment conclusion
1.MTT method cytoactive the selection result confirms: precious imperial refreshment capsule novel formulation and former preparation, be applicable to all strengthening the PC12 cell survival rate by Glu-induced Injury, and novel formulation is better than former preparation under concentration.
2. compare with former preparation; novel formulation can significantly reduce LDH and NO content in culture fluid, increased SOD level, and the preparation of prompting embodiment 1 can reduce neural cell injury degree; the neurocyte of Glu-induced Injury is had to certain protective effect, and effect is better than former preparation.
Experimental example 2, ethanol is caused to the impact experiment that learning and memory of little mouse reproduces disappearance
One, experiment material:
1, the precious imperial refreshment capsule of the preparation of precious imperial refreshment capsule novel formulation: embodiment 1;
2, the former preparation of precious imperial refreshment capsule (hereinafter to be referred as former preparation): the imperial refreshment capsule of commercially available treasure (Qinghai gold is scolded Tibetan medicine Pharmaceutical limited company), lot number: 20090908.
3, positive control medicine: piracetam, Jiangxi Jin Yao pharmaceutcal corporation, Ltd, lot number: 100612.
4, ethanol: Tianjin Guang Cheng chemical reagent company limited, product batch number: 20110915.
5, DJ-200 diving tower auto testing instrument: Chengdu TME Technology Co., Ltd. produces.
Two, experimental technique
Get 50 of healthy mices, male and female half and half, body weight 18～22g, is divided into 5 groups at random, is respectively blank group, percent by volume 40% ethanol model group, the western smooth 0.8g/kg group of pyrrole rubbish, precious imperial refreshment novel formulation 0.5g/kg and former preparation 0.5g/kg group.Each organizes gavage (ig) administration, every day 1 time, and totally 10 days, blank group and model group gavage (ig) same volume distilled water, after administration in the 9th day, 2h puts into diving tower instrument by mice and trains 5min; The next day of gavage (ig) administration 1 time again, the ethanol 10ml/kg of gavage after 1.5h (ig) percent by volume 40%, blank group gavage (ig) same volume distilled water, in batches parallel after 30min mice is put on the copper grid in diving tower instrument, energising 5min (Control of Voltage is at 24V) also records mice both feet net-fault number of times, is and jumps off number of times.Result of the test with
represent, adopt one factor analysis of variance and LSD to organize mean more and compare between two.P < 0.05, for there being significant difference, the results are shown in Table 5.
Three, experimental result
The effect (diving tower method) of table 5 pair ethanol induced mice memory acquisition disturbance (
n=10)
Note: with the comparison of blank group, * * P < 0.01; With model group comparison, Δ P < 0.05
Table 5 result shows: the former preparation 0.5g/kg of precious imperial refreshment and novel formulation 0.50g/kg can obviously reduce the errors number being caused by ethanol and increase, and point out this medicine to have good improvement effect to ethanol induced mice memory represents disappearance, and novel formulation is better than former preparation.
Experimental example 3, the impact experiment on Anisodine induced mice memory acquisition disturbance
One, experiment material:
1, the precious imperial refreshment capsule of the preparation of precious imperial refreshment capsule novel formulation: embodiment 1;
2, the former preparation of precious imperial refreshment capsule (hereinafter to be referred as former preparation): the imperial refreshment capsule of commercially available treasure (Qinghai gold is scolded Tibetan medicine Pharmaceutical limited company), lot number: 20090908.
3, positive control medicine: piracetam: Jiangxi Jin Yao pharmaceutcal corporation, Ltd, lot number: 100612.
4, Anisodine: provided by Sigma chemical CO..
5, DJ-200 diving tower auto testing instrument: Chengdu TME Technology Co., Ltd. produces.
Two, experimental technique
Get 50 of healthy mices, male and female half and half, body weight 18～22g, is divided into 5 groups at random, is respectively blank group, Anisodine model group, the western smooth 0.8g/kg group of pyrrole rubbish, the former preparation 0.5g/kg of precious imperial refreshment and novel formulation 0.5g/kg group.Each organizes gavage (ig) administration, every day 1 time, totally 10 days, blank group and model group gavage (ig) same volume distilled water.After administration in the 9th day, 2h respectively organizes lumbar injection (ip) Anisodine aqueous solution 5mg/kg except blank group, after 10min, mice is put into diving tower instrument endoadaptation 3min, then mice is placed on copper grid to energising 5min, the memory training of shocking by electricity.Next day, gavage (ig) administration 1 time again, after 2h was put in mice on the copper grid in diving tower instrument, and energising 5min (Control of Voltage is at 24V) records mice both feet net-fault number of times in 5min, be and jump off number of times, result of the test with
represent, adopt one factor analysis of variance and LSD to organize mean more and compare between two.P < 0.05, for there being significant difference, the results are shown in Table 6.
Three, experimental result
The effect (diving tower method) of table 6 pair Anisodine induced mice memory acquisition disturbance (
n=10)
Note: with the comparison of blank group, * P < 0.05; With model group comparison, Δ P < 0.05
Table 6 result shows: precious imperial refreshment novel formulation group 0.50g/kg can obviously reduce mouse wrong times in 5min and increase, show that its mouse brain that Anisodine is caused remembers acquired obstacle tool and improve significantly, point out precious imperial refreshment to there is the effect of obvious enhancing learning and remembering ability, and novel formulation is better than former preparation.
Embodiment 2, a kind of preparation for the treatment of the medicament composition granule agent of apoplexy sequela
(1) volatile oil extracts and enclose: by crude drug composition and ratio, get Fructus Piperis Longi 435g, Flos Caryophylli 485g, Semen Myristicae 435g, Fructus Amomi Rotundus 435g, Fructus Tsaoko 325g, Cuminum celery 270g, Lignum Santali Albi 435g, Semen Nigellae 270g, Lignum Aquilariae Resinatum 865g, Fructus Malvae 865g, Cortex Cinnamomi 865g, Radix Aucklandiae 1080g, Lignum pterocarpi indici 1080g, Rhododendron 325g, totally 14 taste medical materials mix, by 4 water extraordinarily of 14 taste medical material gross weights, employing steam distillation, extract volatile oil, extract 3h, collect volatile oil, obtain volatile oil 19ml, medicinal liquid filters, and obtains extracting solution A and medicinal residues A;
Gained volatile oil is added in the beta cyclodextrin saturated aqueous solution of percent weight in volume 3%, the envelope-bulk to weight ratio of volatile oil and beta cyclodextrin is 1ml: 5g, under stirring condition, keeps temperature 60 C, stir 4h ,-4 ℃ of cold preservations are spent the night, sucking filtration, precipitation, 50 ℃ of vacuum dryings, obtain volatile oil clathrate compound;
(2) ethanol extraction: press crude drug composition and ratio extracting liquorice 650g, Lagotis brachystachya Maxim. 2165g, Fructus Choerospondiatis 325g, Corydalis impatiens (Pall.) Fisch. 650g, Fructus Chebulae 1405g, Fructus Phyllanthi 1080g, Fructus Terminaliae Billericae (enucleation) 865g, totally 7 taste medical materials, medicinal residues A after extracting volatile oil with step (1) mixes, add volume by volume concentration 60% ethanol water reflux, extract, 2 times, the amount that adds for the first time ethanol is described 7 taste medical materials and medicinal residues A gross weight 8 times, extract 2h, the amount that adds for the second time ethanol is 8 times of weight portions of described 7 taste medical materials and medicinal residues A gross weight, extract 2h, filter, merge medicinal liquid and obtain ethanol extraction liquid, concentrating under reduced pressure, dry, obtain ethanol extraction and medicinal residues B,
(3) water extraction: the medicinal residues B after above-mentioned steps (2) ethanol extraction, extracting in water 2 times, the weight that adds for the first time water is 8 times of medicinal residues B weight, extract 2h, the weight that adds for the second time water is 9 times of medicinal residues B weight, extracts 2h, filters, merge medicinal liquid and obtain extracting solution B, this extracting solution B and step (1) are extracted to the extracting solution A merging after volatile oil, and concentrating under reduced pressure, is concentrated into the fluid extract that under 60 ℃ of conditions, relative density is 1.12, dry, obtain water extract;
(4) medical material fine powder is pulverized: in above-mentioned raw materials medicine ratio, get Margarita 865g, Concretio Silicea Bambusae 110g, Stigma Croci 435g, Eriocheir sinensis 540g, Lapis Micae Aureus 435g, iron powder (system) 215g, artificial Calculus Bovis 110g, Moschus 110g, totally 8 taste medical materials, pulverize, obtain medical material fine powder;
(5) preparations shaping: the volatile oil clathrate compound that above-mentioned steps (1) is obtained to (4), ethanol extraction, water extract and medical material fine powder mix, get Zhen Long refreshment extract, according to common process, the Icing Sugar and the 2%-5% hydroxypropyl emthylcellulose (HPMC) that add 5 times of weight portions of precious imperial refreshment extract, mix, with volumetric concentration 80% alcohol granulation, dry, every packed 2g, obtains.
Embodiment 3, a kind of preparation for the treatment of the medicinal composition tablets of apoplexy sequela
(1) volatile oil extracts and enclose: by crude drug composition and ratio, get Fructus Piperis Longi 435g, Flos Caryophylli 485g, Semen Myristicae 435g, Fructus Amomi Rotundus 435g, Fructus Tsaoko 325g, Cuminum celery 270g, Lignum Santali Albi 435g, Semen Nigellae 270g, Lignum Aquilariae Resinatum 865g, Fructus Malvae 865g, Cortex Cinnamomi 865g, Radix Aucklandiae 1080g, Lignum pterocarpi indici 1080g, Rhododendron 325g, totally 14 taste medical materials mix, by 8 water extraordinarily of 14 taste medical material gross weights, employing steam distillation, extract volatile oil, extract 6h, collect volatile oil, obtain volatile oil 22ml, medicinal liquid filters, and obtains extracting solution A and medicinal residues A;
Gained volatile oil is added in the beta cyclodextrin saturated aqueous solution of percent weight in volume 4%, the envelope-bulk to weight ratio of volatile oil and beta cyclodextrin is 1ml: 3g, under stirring condition, keeps 40 ℃ of temperature, stir 6h, 0 ℃ of cold preservation is spent the night, sucking filtration, precipitation, 50 ℃ of vacuum dryings, obtain volatile oil clathrate compound;
(2) ethanol extraction: add Radix Glycyrrhizae 650g in above-mentioned raw materials medicine ratio in the medicinal residues A after above-mentioned steps (1) is extracted volatile oil, Lagotis brachystachya Maxim. 2165g, Fructus Choerospondiatis 325g, Corydalis impatiens (Pall.) Fisch. 650g, Fructus Chebulae 1405g, Fructus Phyllanthi 1080g, Fructus Terminaliae Billericae (enucleation) 865g, totally 7 taste medical materials, add concentration of volume percent 80% ethanol water reflux, extract, 2 times, the amount that adds for the first time ethanol is described 7 taste medical materials and medicinal residues A gross weight 10 times, extract 3h, the amount that adds for the second time ethanol is described 7 taste medical materials and medicinal residues A gross weight 8 times, extract 2h, filter, merge medicinal liquid and obtain ethanol extraction liquid, concentrating under reduced pressure, dry, obtain ethanol extraction and medicinal residues B,
(3) water extraction: the medicinal residues B after above-mentioned steps (2) ethanol extraction, extracting in water 2 times, the weight that adds for the first time water is 10 times, the water of medicinal residues B weight, extract 2h, the weight that adds for the second time water is 8 times of medicinal residues B weight, extracts 2h, filters, merge medicinal liquid and obtain extracting solution B, this extracting solution B and step (1) are extracted to the extracting solution A merging after volatile oil, and concentrating under reduced pressure, is concentrated into the fluid extract that under 60 ℃ of conditions, relative density is 1.12, dry, obtain water extract;
(4) medical material fine powder is pulverized: by crude drug composition and ratio, get Margarita 865g, Concretio Silicea Bambusae 110g, Stigma Croci 435g, Eriocheir sinensis 540g, Lapis Micae Aureus 435g, iron powder (system) 215g, artificial Calculus Bovis 110g, Moschus 110g, totally 8 taste medical materials, be crushed to fine powder, obtain medical material fine powder;
(5) preparations shaping: the volatile oil clathrate compound that above-mentioned steps (1) is obtained to (4), ethanol extraction, water extract and medical material fine powder mix, get Zhen Long refreshment extract, according to common process, add appropriate starch, microcrystalline Cellulose, magnesium stearate, mix, with percent by volume 80% ethanol water, granulate, dry, tabletting, every 0.30g, sugar coating or film-coat, obtain.
Claims (4)
1. a preparation method for the treatment of the drug combination preparation of apoplexy sequela, the raw material medicines in portions by weight of described pharmaceutical composition consists of: 17.3 parts of Margaritas, 2.2 parts of Concretio Silicea Bambusaes, 8.7 parts of Stigma Crocis, 9.7 parts of Flos Caryophyllis, 8.7 parts of Semen Myristicaes, 8.7 parts, Fructus Amomi Rotundus, 6.5 parts of Fructus Tsaokos, 8.7 parts, Lignum Santali Albi, 21.6 parts of Lignum pterocarpi indici, 17.3 parts of Lignum Aquilariae Resinatum, 28.1 parts of Fructus Chebulaes, 17.3 parts of Fructus Terminaliae Billericaees, 21.6 parts of Fructus Phyllanthis, 21.6 parts of the Radix Aucklandiae, 17.3 parts of Cortex Cinnamomis, 8.7 parts of Fructus Piperis Longi, 10.8 parts of Eriocheir sinensiss, 8.7 parts of Lapis Micae Aureuses, 5.4 parts of Cuminum celerys, 2.2 parts of artificial Calculus Boviss, 2.2 parts, Moschus, 6.5 parts of Fructus Choerospondiatis, 6.5 parts of Rhododendrons, 13.0 parts of Corydalis impatiens (Pall.) Fisch.s, 43.3 parts of Lagotis brachystachya Maxim.s, 4.3 parts of Magnetite (processed), 17.3 parts of Fructus Malvae, 13.0 parts, Radix Glycyrrhizae, 5.4 parts of Semen Nigellaes, comprise the following steps:
(1) by crude drug composition and ratio, get the totally 14 taste medical materials mixing of Fructus Piperis Longi, Flos Caryophylli, Semen Myristicae, Fructus Amomi Rotundus, Fructus Tsaoko, Cuminum celery, Lignum Santali Albi, Semen Nigellae, Lignum Aquilariae Resinatum, Fructus Malvae, Cortex Cinnamomi, the Radix Aucklandiae, Lignum pterocarpi indici, Rhododendron, by 4～8 water extraordinarily of 14 taste medical material gross weights, adopt steam distillation, extract volatile oil, extract 3～6h, collect volatile oil, obtain volatile oil, medicinal liquid filters, and obtains extracting solution A and medicinal residues A;
Gained volatile oil is added in the beta cyclodextrin saturated aqueous solution of percent weight in volume 3-4%, the envelope-bulk to weight ratio of volatile oil and beta cyclodextrin is 1ml:3-5g, under stirring condition, keep 40 ℃-60 ℃ of temperature, stir 3～4h ,-4 ℃ of-4 ℃ of cold preservations are spent the night, sucking filtration, precipitation, 40 ℃ of-60 ℃ of vacuum dryings, obtain volatile oil clathrate compound;
(2) press crude drug composition and ratio extracting liquorice, Lagotis brachystachya Maxim., Fructus Choerospondiatis, Corydalis impatiens (Pall.) Fisch., Fructus Chebulae, Fructus Phyllanthi, Fructus Terminaliae Billericae totally 7 taste medical materials, medicinal residues A after extracting volatile oil with step (1) mixes, alcoholic solution reflux, extract, 2-3 time that adds volumetric concentration 60～100%, the amount that at every turn adds ethanol is described 7 taste medical materials and medicinal residues A gross weight 8-10 times, extracts 2-3h, filters, merge medicinal liquid and obtain ethanol extraction liquid, concentrating under reduced pressure, dry, obtain ethanol extraction and medicinal residues B;
(3) the medicinal residues B after above-mentioned steps (2) ethanol extraction, extracting in water 2-3 time, the weight that at every turn adds water is 8-10 times of medicinal residues B weight, extracts 2-3h, filters, and merges medicinal liquid and obtains extracting solution B; This extracting solution B and step (1) are extracted to the extracting solution A merging after volatile oil, and concentrating under reduced pressure, is concentrated into the fluid extract that under 60 ℃ of conditions, relative density is 1.12, dry, obtains water extract;
(4) by crude drug composition and ratio, get Margarita, Concretio Silicea Bambusae, Eriocheir sinensis, Lapis Micae Aureus, Magnetite (processed), Stigma Croci, artificial Calculus Bovis, Moschus totally 8 taste medical materials, pulverize, obtain medical material fine powder;
(5) volatile oil clathrate compound above-mentioned steps (1) being made to (4), ethanol extraction, water extract and medical material fine powder mix, and add conventional adjuvant, according to common process, are prepared into pharmaceutically acceptable any dosage form.
2. a kind of preparation method for the treatment of the drug combination preparation of apoplexy sequela as claimed in claim 1, the raw material medicines in portions by weight of described pharmaceutical composition consists of: 17.3 parts of Margaritas, 2.2 parts of Concretio Silicea Bambusaes, 8.7 parts of Stigma Crocis, 9.7 parts of Flos Caryophyllis, 8.7 parts of Semen Myristicaes, 8.7 parts, Fructus Amomi Rotundus, 6.5 parts of Fructus Tsaokos, 8.7 parts, Lignum Santali Albi, 21.6 parts of Lignum pterocarpi indici, 17.3 parts of Lignum Aquilariae Resinatum, 28.1 parts of Fructus Chebulaes, 17.3 parts of Fructus Terminaliae Billericaees, 21.6 parts of Fructus Phyllanthis, 21.6 parts of the Radix Aucklandiae, 17.3 parts of Cortex Cinnamomis, 8.7 parts of Fructus Piperis Longi, 10.8 parts of Eriocheir sinensiss, 8.7 parts of Lapis Micae Aureuses, 5.4 parts of Cuminum celerys, 2.2 parts of artificial Calculus Boviss, 2.2 parts, Moschus, 6.5 parts of Fructus Choerospondiatis, 6.5 parts of Rhododendrons, 13.0 parts of Corydalis impatiens (Pall.) Fisch.s, 43.3 parts of Lagotis brachystachya Maxim.s, 4.3 parts of Magnetite (processed), 17.3 parts of Fructus Malvae, 13.0 parts, Radix Glycyrrhizae, 5.4 parts of Semen Nigellaes, comprise the following steps:
(1) by crude drug composition and ratio, get the totally 14 taste medical materials mixing of Fructus Piperis Longi, Flos Caryophylli, Semen Myristicae, Fructus Amomi Rotundus, Fructus Tsaoko, Cuminum celery, Lignum Santali Albi, Semen Nigellae, Lignum Aquilariae Resinatum, Fructus Malvae, Cortex Cinnamomi, the Radix Aucklandiae, Lignum pterocarpi indici, Rhododendron, by 6 water extraordinarily of 14 taste medical material gross weights, adopt steam distillation, extract volatile oil, extract 4h, collect volatile oil, obtain volatile oil, medicinal liquid filters, and obtains extracting solution A and medicinal residues A;
Gained volatile oil is added in the beta cyclodextrin saturated aqueous solution of percent weight in volume 4%, the envelope-bulk to weight ratio of volatile oil and beta cyclodextrin is 1ml:4g, under stirring condition, keeps temperature 60 C, stir 4h, 4 ℃ of cold preservations are spent the night, sucking filtration, precipitation, 50 ℃ of vacuum dryings, obtain volatile oil clathrate compound;
(2) press crude drug composition and ratio extracting liquorice, Lagotis brachystachya Maxim., Fructus Choerospondiatis, Corydalis impatiens (Pall.) Fisch., Fructus Chebulae, Fructus Phyllanthi, Fructus Terminaliae Billericae totally 7 taste medical materials, medicinal residues A after extracting volatile oil with step (1) mixes, the ethanol water reflux, extract, 2 times that adds volumetric concentration 90%, the amount that adds for the first time ethanol is described 7 taste medical materials and medicinal residues A gross weight 10 times, extract 2h, the amount that adds for the second time ethanol is described 7 taste medical materials and medicinal residues A gross weight 8 times, extract 2h, filter, merge medicinal liquid and obtain ethanol extraction liquid, concentrating under reduced pressure, dry, obtain ethanol extraction and medicinal residues B;
(3) the medicinal residues B after above-mentioned steps (2) ethanol extraction, extracting in water 2 times, the weight that adds for the first time water is 10 times of medicinal residues B weight, extract 2h, the weight that adds for the second time water is 8 times of medicinal residues B weight, extracts 2h, filters, merge medicinal liquid and obtain extracting solution B, this extracting solution B and step (1) are extracted to the extracting solution A merging after volatile oil, and concentrating under reduced pressure, is concentrated into the fluid extract that under 60 ℃ of conditions, relative density is 1.12, dry, obtain water extract;
(4) by crude drug composition and ratio, get Margarita, Concretio Silicea Bambusae, Eriocheir sinensis, Lapis Micae Aureus, Magnetite (processed), Stigma Croci, artificial Calculus Bovis, Moschus totally 8 taste medical materials, pulverize, obtain medical material fine powder;
(5) volatile oil clathrate compound above-mentioned steps (1) being made to (4), ethanol extraction, water extract and medical material fine powder mix, and add appropriate amount of starch, granulate, dry, incapsulate, and obtain.
3. a kind of preparation method for the treatment of the drug combination preparation of apoplexy sequela as claimed in claim 1, the preparation of granule comprises the following steps:
(1) by crude drug composition and ratio, get Fructus Piperis Longi 435g, Flos Caryophylli 485g, Semen Myristicae 435g, Fructus Amomi Rotundus 435g, Fructus Tsaoko 325g, Cuminum celery 270g, Lignum Santali Albi 435g, Semen Nigellae 270g, Lignum Aquilariae Resinatum 865g, Fructus Malvae 865g, Cortex Cinnamomi 865g, Radix Aucklandiae 1080g, Lignum pterocarpi indici 1080g, Rhododendron 325g, totally 14 taste medical materials mix, by 4 water extraordinarily of 14 taste medical material gross weights, adopt steam distillation, extract volatile oil, extract 3h, collect volatile oil, obtain volatile oil 19ml, medicinal liquid filters, and obtains extracting solution A and medicinal residues A;
Gained volatile oil is added in the beta cyclodextrin saturated aqueous solution of percent weight in volume 3%, the envelope-bulk to weight ratio of volatile oil and beta cyclodextrin is 1ml:5g, under stirring condition, keeps temperature 60 C, stir 4h ,-4 ℃ of cold preservations are spent the night, sucking filtration, precipitation, 50 ℃ of vacuum dryings, obtain volatile oil clathrate compound;
(2) press crude drug composition and ratio extracting liquorice 650g, Lagotis brachystachya Maxim. 2165g, Fructus Choerospondiatis 325g, Corydalis impatiens (Pall.) Fisch. 650g, Fructus Chebulae 1405g, Fructus Phyllanthi 1080g, Fructus Terminaliae Billericae 865g, totally 7 taste medical materials, medicinal residues A after extracting volatile oil with step (1) mixes, add volume by volume concentration 60% ethanol water reflux, extract, 2 times, the amount that adds for the first time ethanol is described 7 taste medical materials and medicinal residues A gross weight 8 times, extract 2h, the amount that adds for the second time ethanol is 8 times of weight of described 7 taste medical materials and medicinal residues A gross weight, extract 2h, filter, merge medicinal liquid and obtain ethanol extraction liquid, concentrating under reduced pressure, dry, obtain ethanol extraction and medicinal residues B,
(3) the medicinal residues B after above-mentioned steps (2) ethanol extraction, extracting in water 2 times, the weight that adds for the first time water is 8 times of medicinal residues B weight, extract 2h, the weight that adds for the second time water is 9 times of medicinal residues B weight, extracts 2h, filters, merge medicinal liquid and obtain extracting solution B, this extracting solution B and step (1) are extracted to the extracting solution A merging after volatile oil, and concentrating under reduced pressure, is concentrated into the fluid extract that under 60 ℃ of conditions, relative density is 1.12, dry, obtain water extract;
(4) in above-mentioned raw materials medicine ratio, get Margarita 865g, Concretio Silicea Bambusae 110g, Stigma Croci 435g, Eriocheir sinensis 540g, Lapis Micae Aureus 435g, Magnetite (processed) 215g, artificial Calculus Bovis 110g, Moschus 110g, totally 8 taste medical materials, pulverize, and obtain medical material fine powder;
(5) volatile oil clathrate compound above-mentioned steps (1) being obtained to (4), ethanol extraction, water extract and medical material fine powder mix, get Zhen Long refreshment extract, according to common process, the Icing Sugar and the 2%-5% hydroxypropyl emthylcellulose (HPMC) that add 5 times of weight portions of precious imperial refreshment extract, mix, with volumetric concentration 80% alcohol granulation, dry, every packed 2g, obtains.
4. treat a preparation method for the drug combination preparation of apoplexy sequela, the preparation of tablet comprises the following steps:
(1) by crude drug composition and ratio, get Fructus Piperis Longi 435g, Flos Caryophylli 485g, Semen Myristicae 435g, Fructus Amomi Rotundus 435g, Fructus Tsaoko 325g, Cuminum celery 270g, Lignum Santali Albi 435g, Semen Nigellae 270g, Lignum Aquilariae Resinatum 865g, Fructus Malvae 865g, Cortex Cinnamomi 865g, Radix Aucklandiae 1080g, Lignum pterocarpi indici 1080g, Rhododendron 325g, totally 14 taste medical materials mix, by 8 water extraordinarily of 14 taste medical material gross weights, adopt steam distillation, extract volatile oil, extract 6h, collect volatile oil, obtain volatile oil 22ml, medicinal liquid filters, and obtains extracting solution A and medicinal residues A;
Gained volatile oil is added in the beta cyclodextrin saturated aqueous solution of percent weight in volume 4%, the envelope-bulk to weight ratio of volatile oil and beta cyclodextrin is 1ml:3g, under stirring condition, keeps 40 ℃ of temperature, stir 6h, 0 ℃ of cold preservation is spent the night, sucking filtration, precipitation, 50 ℃ of vacuum dryings, obtain volatile oil clathrate compound;
(2) in the medicinal residues A after above-mentioned steps (1) is extracted volatile oil, in above-mentioned raw materials medicine ratio, add Radix Glycyrrhizae 650g, Lagotis brachystachya Maxim. 2165g, Fructus Choerospondiatis 325g, Corydalis impatiens (Pall.) Fisch. 650g, Fructus Chebulae 1405g, Fructus Phyllanthi 1080g, Fructus Terminaliae Billericae 865g, totally 7 taste medical materials, add concentration of volume percent 80% ethanol water reflux, extract, 2 times, the amount that adds for the first time ethanol is described 7 taste medical materials and medicinal residues A gross weight 10 times, extract 3h, the amount that adds for the second time ethanol is described 7 taste medical materials and medicinal residues A gross weight 8 times, extract 2h, filter, merge medicinal liquid and obtain ethanol extraction liquid, concentrating under reduced pressure, dry, obtain ethanol extraction and medicinal residues B,
(3) the medicinal residues B after above-mentioned steps (2) ethanol extraction, extracting in water 2 times, the weight that adds for the first time water is 10 times of medicinal residues B weight, extract 2h, the weight that adds for the second time water is 8 times of medicinal residues B weight, extracts 2h, filters, merge medicinal liquid and obtain extracting solution B, this extracting solution B and step (1) are extracted to the extracting solution A merging after volatile oil, and concentrating under reduced pressure, is concentrated into the fluid extract that under 60 ℃ of conditions, relative density is 1.12, dry, obtain water extract;
(4) by crude drug composition and ratio, get Margarita 865g, Concretio Silicea Bambusae 110g, Stigma Croci 435g, Eriocheir sinensis 540g, Lapis Micae Aureus 435g, Magnetite (processed) 215g, artificial Calculus Bovis 110g, Moschus 110g, totally 8 taste medical materials, are crushed to fine powder, obtain medical material fine powder;
(5) volatile oil clathrate compound above-mentioned steps (1) being obtained to (4), ethanol extraction, water extract and medical material fine powder mix, get Zhen Long refreshment extract, according to common process, add appropriate starch, microcrystalline Cellulose, magnesium stearate, mix, with percent by volume 80% ethanol water, granulate, dry, tabletting, every 0.30g, sugar coating or film-coat, obtain.
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| CN104173504B (en) * | 2014-07-25 | 2016-09-21 | 北京汉典制药有限公司 | A kind of Chinese medicine capsules treating diabetic retinopathy and application thereof |
| CN104173506B (en) * | 2014-07-25 | 2016-10-05 | 北京汉典制药有限公司 | The Chinese medical extract of the preparation method of a kind of Chinese medical extract and preparation thereof and purposes |
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| CN104173503B (en) * | 2014-07-25 | 2016-10-05 | 北京汉典制药有限公司 | The Chinese herbal granules of the preparation method of a kind of Chinese herbal granules and preparation thereof and purposes |
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| CN105770685B (en) * | 2014-12-23 | 2019-06-04 | 金诃藏药（山东）健康产业有限公司 | A kind of preparation method of pharmaceutical composition that treating apoplexy |
| CN111714461A (en) * | 2020-07-07 | 2020-09-29 | 云南中医药大学 | Amomum tsao-ko volatile oil inclusion compound oral tablet and preparation method thereof |
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